Today, more than ever, ophthalmologists are being asked to answer patients’ questions about vitamin supplements and nutrition. The importance of diet and eye health is not new. The need to obtain adequate vitamin A to prevent xerophthalmia and night-blindness, particularly where malnutrition is rampant, has been known for decades (reviewed by Underwood and Arthur1). More recently, interest has been directed at whether nutritional supplements might prevent loss of vision caused by degenerative conditions that become more common as we age, such as cataract and macular degeneration.
The benefits of nutritional supplements may have broad public health importance. Results of the Age-Related Eye Disease Study (AREDS) suggest that nutritional supplements may be one of the most promising means discovered, to date, of delaying end-stage age-related macular degeneration (AMD), the most common cause of blindness among older people in developed countries.
There is some interest in the possibility that supplements might slow the progression of diabetic retinopathy, the number 1 cause of blindness among working-age people. Moreover, some studies (reviewed herein) suggest that supplements might slow the development of cataract, which affects more than half of us by age 75 years.
In addition, surgery for cataracts is expensive, accounting for more than 12% of the Medicare budget, which was last evaluated in 1992.
As these age-related conditions become more prevalent in a population that is aging,8 the potential public health benefits of supplements are large. However, scientific evidence to support these benefits is stronger in some cases than others.
The purpose of this review is to provide guidelines for clinical practice in recommending the use of nutritional supplements for reducing the development of eye diseases that are common among older people, based on the current evidence. While supplementation may be considered in the treatment of rarer inherited retinal degenerations, this will not be considered in the current review. Benefits of several specific types of supplements that are commonly available for slowing the development of common eye diseases and risks are considered in separate sections that follow. We also discuss issues for clinicians to consider as more scientific evidence becomes available, from the many studies that are expected to emerge during the next few years.
Ultimately, any physician hopes to improve the overall health and wellbeing of patients, rather than merely focus on eye health. Therefore, we will also briefly consider the evidence that describes the benefits and risks of supplements to overall health. For a thoughtful and more thorough discussion of this larger topic, we refer readers to the recent article by Willett and Stampfer.
Extreme deficiencies of many vitamins and minerals have been shown to cause cataract or retinal dysfunction in experimental animals, particularly under extreme experimental conditions in the laboratory. In humans, the results of epidemiologic studies are needed to determine whether more modest fluctuations of vitamins and minerals influence age-related degenerative conditions under the conditions that are unique to people. Studies of large and diverse populations provide an estimate of the magnitude of impact that changes in vitamins and supplements have on the risk of common eye diseases, relative to other medical or lifestyle changes that can be recommended to patients (such as stopping smoking, controlling hypertension, losing weight, etc). Results of observational investigations and clinical trials are summarized in the following sections.
Benefits to Eyes:
Multivitamins usually contain all essential vitamins that one would expect to get from foods at levels that meet the nutrient requirement of nearly all healthy individuals. These nutrient levels are the highest requirement of the recommended dietary allowances (RDAs) for specific age and sex groups.12 Many, but not all, also contain the essential minerals at levels that we typically get from food. The RDAs are set at levels that are judged by panels of scientists to be those needed to promote health in most groups of healthy people. However, they may not be adequate for individuals with unique needs caused by the presence of disease.
Observational studies in 8 different populations indicate lower rates of cataract or cataract extraction among people who use multivitamin supplements, compared with only 2 studies that observed no association. However, in the absence of randomized controlled clinical trials, there is no proof, at this time, that multivitamins lower the risk of cataract. The possibility exists that other aspects of a healthy lifestyle among supplement users explain the lower rates of cataracts in the observational studies.
Unfortunately, we may never have the guidance of clinical trials to answer the questions of the benefits of multiple supplements on cataract in the American population. If multivitamins do lower risk, as the observational studies consistently suggest, then many years may be required to observe a benefit in clinical trials— yet, such trials are generally conducted for less than 10 years.
To date, there are results of only one clinical trial of multivitamin supplements. This trial, in a malnourished population in China,15 tested the influence of using multi-vitamins for 5 years on the prevalence of cataract. A lower prevalence of cataract was observed in users than nonusers of multivitamins, among persons 65 to 74 years of
age (but not among persons 45 to 64 years of age).
The results of this 5-year study suggest that short-term effects may be possible. Considered in conjunction with observational studies in which only long-term supplementation was associated with lower risk, these results suggest that short-term effects might be limited to malnourished populations. This result will not likely be duplicated in the United States, because people with poor diets are not usually subjects in clinical trials. If the influence of multi-vitamins on cataract is gradual, over many years, or limited to people with very poor diets, then the possible benefits of multivitamins on cataract are not likely to be experimentally proved.
A 9-year, randomized, placebo-controlled clinical trial of the influence of multivitamin supplementation on cataract development and progression is currently under way in Italy in about 1000 people. This study is likely to provide new in-sights. Also, in the next 5 to 10 years, the results from many long-term prospective observational studies that are currently under way will provide future insights about whether multivitamins themselves or other associated lifestyles are responsible for lower cataract risk among people who use supplements. If people who take multivitamin supplements consistently have a lower risk of cataract across many different segments of a population, then there is a lower possibility that the apparent beneficial effect is caused by other unrevealed factors.
In contrast, there is no evidence that use of multivitamins slows the onset or progression of AMD, although it has been investigated in several populations. This may be because people who begin to show signs of developing macular degeneration may decide or be advised to start taking nutritional supplements.
This change in supplement use (depending on having signs of the conditions) may confound relationships of long-term supplement use to age-related maculopathy. This would make it difficult to observe a protective association if one existed. Such uncontrolled confounding or noise, inherent in any epidemiologic study, may overwhelm any small beneficial effect. It remains conceivable that multivitamins may ensure adequacy of intake of several nutrients that are important to the health of the retina and retinal pigment epithelium.
However, evidence of beneficial effect may be hard to generate because supplementation is common, particularly in people who have a family history of early signs of macular degeneration.